Download Infections of the lymphatic system

24.1
CHAPTER 24
Infections of the lymphatic system
Wayne Melrose and John M. Goldsmid
24.1
INTRODUCTION
The lymphatic system can be involved in a wide range of infectious conditions, viral,
bacterial, mycotic and parasitic. Mostly this involvement is transient, the lymphatic
system serving as part of the route utilized by micro-organisms in their spread throughout
the body1. As such, enlargement of the lymph nodes may often reflect the spread of an
infection from a local entry point1.
However, in many infections the effect on the lymphatics may be both consistent and
clinically marked. The lymphadenopathy may be local or generalized and
lymphadenopathy is or can be a significant feature of acute HIV infection, primary
Herpes simplex, some rickettsial infections, tularaemia, plague, cat-scratch fever due to
Bartonella henselae, primary syphilis, lymphogranuloma venereum, chancroid,
leptospirosis, brucellosis, relapsing fever, African trypanosomiasis (e.g. Winterbottom’s
Sign), Chagas’ disease, and leishmaniasis2. Charters 3 also lists schistosomiasis (during
the Katayama phase), paragonimiasis, onchocerciasis, trichinosis, leprosy, and
sporotrichosis as causes of lymphadenopathy. However, the most significant and
noteworthy involvement of the lymphatic system is seen in the Glandular Fever
Syndrome and in Lymphatic filariasis. It is these two conditions, which will be dealt with
in detail.
24.2
GLANDULAR FEVER SYNDROME
The Glandular Fever Syndrome (GFS) has been overviewed by Mills and Goldsmid4 and
is a condition characterised by fever, the presence of atypical lymphocytes in the
peripheral blood, sore throat (often with exudate), splenomegaly, lymphadenopathy (local
or generalised), liver dysfunction, malaise and sometimes a rash1,4,5. The infectious
components of GFS comprise the Epstein Barr Virus (EBV) which specifically causes the
condition of Infectious Mononucleosis, Cytomegalovirus (CMV), and the protozoan
Toxoplasma gondii. Acute HIV may also present in this way. Of these causative
organisms, EBV is the one most commonly associated with GFS – although in the
tropics, infectious mononucleosis is not often seen and EBV is better known for it’s
association with Burkitt’s lymphoma in Africa and Papua New Guinea and
nasopharyngeal carcinoma in China and SE Asia. EBV infection can also be associated
uncommon late tumours and with lymphoma in the immunologically compromised. It is
believed that clinical Infectious Mononucleosis is rarely seen in the tropics due to
infection occurring (mostly subclinically) at a very young age5. The effects of CMV and
INFECTIONS OF THE LYMPHATIC SYSTEM
24.2
T. gondii on the foetus can be disastrous if a previously unexposed woman acquires the
infection while pregnant.
Of these organisms, EBV is transmitted by salivary exchange and kissing; CMV by
intimate contact and crowding of young children which facilitates transmission and by
sexual contact in adolescents and young adults; HIV sexually and T. gondii from eating
vegetables or drinking water contaminated with the oocysts passed by cats or, more
commonly, from the ingestion of intermediate hosts of the protozoan (mutton, pork,
chicken and less commonly beef as well as a host of non-domesticated animals that might
make up part of the diet in regional situations - see Chapter 4).
Diagnosis of the GFS depends on the aetiological agent. Mostly, diagnosis is confirmed
by antibody serology. Thus EBV infection is confirmed by specific antibody tests;
heterophile antibody tests such as the Monospot Test, or by PCR.
Treatment of IM and CMV is mostly supportive with bed rest, although Burkitt’s
lymphomas and nasopharyngeal carcinomas respond well to standard antineoplastic
drugs4. Aids can be treated as described in Chapter 9. Severe and clinically apparent T.
gondii can be treated with sulphadiazine and pyrimethamine or spiramycin6-8
Clindamycin has also been found to be effective but should be reserved for cases of
severe toxoplasmosis8. The dosages recommended are:
1) Pyremethamine: Adult: 25-100 mg/d orally for 3-6 weeks
(Child: 1-2mg/kg/d orally up to 25mg for 3-6 weeks)
+
Sulphadiazine: Adult: 1 – 1.5g orally (or iv) qid for 3-6 weeks
(Child: 50mg/kg orally up to adult dose.qid for 3-6 weeks)
Folate supplements are usually added with this regimen.
2)
Spiramycin (For pregnant women if needed or for patients sensitive to sulphas):
Adult: 3-4g/d
3)
Clindamycin: 600mg orally qid for 3-6 weeks.
(Sheorey, Walker and Biggs (2000) in Clinical Parasitology, Melbourne University Press,
also mention the use of albendazole as an alternative treatment for toxoplasmosis))
In ocular toxoplasmosis, corticosteroids should also be used.
24.3
FILARIAL INFECTIONS INVOLVING THE LYMPHATIC SYSTEM
Filarial parasites (filaroids) are long hair-like tissue-dwelling nematodes. All except the
Guinea worm Dracunculus medinensis (which uses a copepod) employ insects as
intermediate hosts. They all have a similar life cycle that includes an obligatory
maturation stage in a blood-sucking insect or a copepod, and a reproductive stage in the
INFECTIONS OF THE LYMPHATIC SYSTEM
24.3
tissues or blood of a definitive host 9. A representative life cycle, Wuchereria bancrofti, is
shown in Figure 24.1.
Figure 24.1. Typical filaroid life cycle (CDC/DPDx, used with permission).
(http://www.dpd.cdc.gov/dpdx)
Adult male and female worms live in the lymphatics, skin, or other tissues. Microfilariae
(which are specialised embryos not larvae) are produced by the female worm, circulate in
the blood, (Figures 24.1, 24.2 and 24.3) or invade the skin, and are ingested by the vector
where larval development, but not multiplication, occurs.
The infective L3 stage migrates to the proboscis of the vector and is transmitted to the
new host during feeding. Unlike malaria, the infective stage is not directly injected into
the skin of the new host. They are deposited onto the skin whilst the mosquito is feeding
and find their own way through the skin, usually via the puncture made by the mosquito.
In Wuchereria bancrofti, Brugia malayi, B. timori and the subcutaneous species from
West Africa (Loa loa), the microfilariae are surrounded by a sheath which appears as a
pale, balloon-like structure in stained preparations. In the other species, the microfilariae
INFECTIONS OF THE LYMPHATIC SYSTEM
24.4
are unsheathed.
Figure 24.2. Microfilaria of W. bancrofti in thick blood film stained with Giemsa stain
and showing the nuclear column (X200).
Figure 24.3. Microfilaria of W. bancrofti in thin blood film attained with Giemsa stain
and showing the sheath (X200)
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There are nine species of filaroid parasites that commonly cause human disease and their
characteristics are summarised in Table 24.1
Species
Disease
Vector
W. bancrofti
Lymphatic
filariasis
“
“
Loiasis
Mansonellosis
Mosquito
Brugia malayi
Brugia timori
Loa loa
Mansonella
perstans
Mansonella
ozzardi
____________
Mansonella
streptocerca
Onchocerca
volvulus
Dracunculus
medinensis
(Guinea worm)
“
____________
“
Onchocerciasis
Dracunculiasis
“
“
Chrysops fly
Midges
Location of
adults
Lymphatic
system
“
“
Migratory
Serous cavities
Location of
microfilariae
Blood
Midge or
Simulid fly
____________
Midge
Thoracic or
peritoneal
cavities_______ ____________
Subcutaneous
Skin
Simulid
blackfly
Copepod
Subcutaneous
nodules
Subcutaneous
tissues
“
“
“
Blood and
serous effusions
Blood
Skin
None. 1st stage
larvae are
liberated into
water
Table 24.1. The filaroid parasites of humans
24.3.1 Lymphatic filariasis
Lymphatic filariasis is a mosquito-borne parasitic disease that is caused by three species
of tissue dwelling filaroids: Wuchereria bancrofti is responsible for 90% of cases and is
found throughout the tropics and in some sub-tropical areas world-wide. Brugia malayi
is confined to Southeast and Eastern Asia. Brugia timori is found only in Timor and its
adjacent islands. All three species cause similar disease. B. malayi is also found in
monkeys, cats and other small animals but it is not known how important this is in the
epidemiology of human disease. Unlike malaria where the only vectors are Anopheline
mosquitoes, lymphatic filariasis can be transmitted by various species of the genera
Anopheles, Culex, Aedes, Ochlerotatus, and Mansonia. The biting-time of the mosquito
correlates with the periodicity of the microfilariae. In most parts of the world, the vectors
are nocturnal feeders and the microfilariae exhibit nocturnal periodicity, where they are
present in the blood in the greatest number around midnight. In areas such as the Central
Pacific where the mosquito feeds during the day, there is a diurnal periodicity where the
highest number of microfilariae occurs at midday. In some areas of Southeast Asia, a sub-
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24.6
periodic pattern is found, where some microfilariae are found in the blood at all times but
there is a nocturnal peak.
Lymphatic filariasis has a long history which reaches back into antiquity. Despite this, it
has been a disease, which up to recent times, has been poorly understood and largely
ignored by health authorities who are struggling to control what were perceived to be
more important vector-borne diseases such as malaria and dengue fever. In the last two
decades or so there has been a flurry of filariasis research, which has provided new
insights into the global burden of filariasis, the pathogenesis and extent of filarial disease,
diagnosis, and control 10,11. Lymphatic filariasis is classified by the World Health
Organisation (WHO) as the second leading cause of permanent and long-term disability
after mental illness 12. In addition to the physical problems, there are severe social and
psychological consequences, especially in those who suffer from disfiguring
complications such as elephantiasis or hydrocele 12-14. Lymphatic filariasis also has a
huge economic impact upon endemic communities. In addition to the direct costs
incurred in medical or surgical treatment, there are enormous indirect costs resulting from
reduced work capacity and labour loss due to the frequency and severity of acute attacks
and the disability due to chronic manifestations of the disease 12 .The total global burden
of lymphatic filariasis is not known and mapping of its endemicity and prevalence is ongoing. Around 83 countries are known to be endemic but distribution mapping is
continuing and more endemic areas are being identified. The most recent estimate puts
the global burden at about 120 million 15. The true figures are certainly higher for
Bancroftian filariasis because most country surveys done in the past were based on the
demonstration of microfilariae. More recent surveys using antigen detection have shown
that surveys of microfilaraemia alone can under-estimate the prevalence by as much as
30% 16. The WHO estimates that of that 120 million, 44 million have overt clinical
disease – lymphodema, elephantiasis, and hydrocele. Another 76 million have covert,
pre-clinical damage to their lymphatic and renal systems. Millions also suffer from
debilitating acute attacks of filarial fevers and lymphadenitis 12.
Until quite recently it was generally accepted that three groups of people are found in
filarial- endemic areas: Those who are exposed, but with no evidence of disease - so
called "endemic normals”, those with “asymptomatic microfilaraemia”, and those with
“chronic pathology” - lymphodema, elephantiasis, or hydrocele. In some areas, most
notably in Asia, another manifestation of filariasis arises - Tropical pulmonary
eosinophilia 17-20. The term "endemic normal" is used to describe those who, despite
constant exposure to filariasis, do not appear to become infected. Whether some of these
people are truly immune to filariasis is debatable 21. Many of these so called "endemic
normals" have a cryptic infection because they have circulating filarial antigen that is
identical to that found in people with microfilaraemia 22, and ultrasound examination can
detect adult worms in the scrotum of some “endemic normal” males 23,24. Asymptomatic
microfilaraemia” is the most common manifestation of filariasis and this situation may
persist for decades without progression to overt clinical disease. Recent studies prove that
“asymptomatic microfilaraemia” is not a benign phase. Approximately half of the men
with “asymptomatic microfilaraemia” have nests of motile adult worms in their scrotal
lymphatics (the "filarial dance sign") and lymphoscintigraphy shows that their lymphatics
INFECTIONS OF THE LYMPHATIC SYSTEM
24.7
are markedly dilated with collateral channelling and increased lymph flow 24-26. Another
very important complication is renal dysfunction caused by direct mechanical damage to
renal blood vessels by microfilariae, or by immune complexes being laid down in the
kidney and manifesting as proteinuria and haematuria27-28. Like many other parasites,
filaroids induce a degree of immunosuppression in their hosts as a means of ensuring
their survival. The reduction in immune responses is not limited to filarial antigens alone
and extends to a range of other antigens including tetanus toxoid 29,30, Salmonella typhi 29,
H and O antigens of TAB vaccine 31, and purified protein derivative (tuberculin) 32,33.
These findings strongly suggest that filarial infection may have an impact upon the
efficacy of vaccination and further research is urgently required.
24.3.2 “Chronic filarial pathology.”
Overall, hydrocele is the most common form of chronic Bancroftian filariasis and in parts
of Africa it predominates. Hydrocele is said to have affected up to 70% of males along
the Tanzanian coast and 60% of males in coastal Kenya by the time they reach age 70
years 34,35. Hydrocele can reduce work capacity, impair sexual activity and enjoyment,
and cause severe psycho-social problems in affected males 14,,36-38. The most feared
complications of lymphatic filariasis are chronic lymphodema and elephantiasis 12-14. In
some populations, despite a high prevalence of microfilaraemia and filarial antigenaemia,
filariasis is a mostly a cryptic disease and the number of people with elephantiasis is
relatively low. For instance, the prevalence of filarial antigenaemia in many parts of
Papua New Guinea is around 80% yet elephantiasis occurs only in scattered foci and is
nowhere common 10. The first manifestation of impending elephantiasis is transient
lymphodema which resolves with limb elevation. This is followed by persisting
lymphodema, then fibrous infiltration and thickening of the skin with fissure and ulcer
formation. The changes grow steadily worse until the limb becomes grossly swollen and
hideously deformed, and normal function is impossible. The evolution of filarial infection
and progression to chronic lymphodema and elephantiasis is not completely understood
and is a complex interaction between transmission intensity, host and parasite immunobiology, in-utero exposure to parasite antigens, secondary infections (see below), and
most probably host and parasite genetics. The shift from “asymptomatic microfilaraemia”
to elephantiasis is accompanied by profound changes in cellular and humoral immunity.
In microfilaraemics, most of the antifilarial antibody is of the IgG4 isotype with smaller
amounts of IgG1, IgG2, IgG3 and IgE. In elephantiasis the proportion of IgG4 decreases
and IgG1, IgG2, IgG3 and IgE increase. There is also an “awakening” of the previously
suppressed cellular immune reactions to filarial and other antigens, but it is not clear
whether the changes in the antibody profile and cellular immunity contribute to the
pathology, or are the result of the pathology. 10,11. What is not in dispute is the role that
acute attacks caused by secondary bacterial and fungal infections have in promoting the
progression to elephantiasis. Active steps to improve hygiene, treat skin lesions with
topical antibacterial and antifungal agents, aggressive antibiotic therapy of systemic
infections, together with exercise and limb elevation can reduce the acute attacks, slow or
prevent progression 40-42. An excellent practical handbook on the diagnosis, staging, and
treatment of filarial lymphodema has been produced and should be on the bookshelf of
everyone who cares for patients with lymphatic filariasis43.
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24.8
24.3.4 Acute filarial disease
Acute filarial attacks can occur in both amicrofilaraemics and microfilaraemics, and are
common in people with chronic filarial pathology 44. They can be extremely painful and
debilitating and many people are confined to their houses and are unable to take part in
productive activity. In some cases filarial infection markers such as filarial antigen and
antifilarial antibody are absent. A possible explanation in these cases is an inflammatory
response against in-coming L3 larvae before the adult worm has become established, but
as yet there is no experimental evidence to support this hypothesis 45. Two distinct
syndromes cause acute attacks 44. The first is called acute dermatolymphangioadenitis
(ADLA), where there is development of a plaque-like lesion of cutaneous or subcutaneous inflammation. This may be accompanied by ascending lymphangitis and
regional adenitis and typical systemic manifestation of bacteraemic such as chills and
fevers are usually present. There is often oedema of the affected limb. This may
completely or partially regress after the acute attack subsides but as noted above,
recurrent ADLA is an important cause of chronic lymphodema. The other syndrome is
called acute filarial lymphangitis (AFL) and is believed to be the result of an
immunological reaction to dead or dying adult worms that have either been killed by the
immune system or chemotherapy. In contrast to ADLA, AFL presents as a distinct wellcircumscribed nodule or cord and there may be local lymphadenitis with lymphangitis
spreading in a centrifugal pattern i.e away from the inflamed lymph node. Fever is not
usually present. These lesions can be extremely painful, and if they are the result of
chemotherapy, can seriously compromise future compliance.
Fortunately such
occurrences are rare. Both ADLA and AFL can occur in the same patient.
24.3.5 Tropical Pulmonary Eosinophilia (TPE)
TPE is most common in Southeast Asia and is at the opposite end of the immunological
spectrum from asymptomatic microfilaraemia because it is the result of a hypersensitivity
response to filarial antigens. There is marked eosinophilia, extreme levels of serum IgE,
and high titres of antifilarial IgG and IgE 11,12. Circulating microfilariae are not usually
found but adult worms may be detected by ultrasound 46. Clinically TPE is characterised
by nocturnal coughing and asthma. Pulmonary infiltration gives rise to a characteristic xray picture called "snow flake" lung. Signs and symptoms resolve quite quickly after
treatment with antifilarial drugs.
24.3.6 Other manifestations of lymphatic filariasis
Chyluria, the passing of milky-coloured urine, is caused by leakage of lymph into the
urinary tract is seen from time to time and is exacerbated by a high-fat diet and exercise.
Filariasis can present with rheumatic features and mono-arthritis of a knee or ankle joint
that resolves after antifilarial treatment is common in filarial-endemic areas, especially in
children. Lymphatic filariasis has also been associated wide spectrum of other clinical
signs and symptoms by various investigators. In some of these the connection is
INFECTIONS OF THE LYMPHATIC SYSTEM
24.9
somewhat tenuous and a direct causal relationship between filarial infection and the other
diseases have not been established 46-48.
24.3.7 Lymphatic filariasis in expatriates and travellers
Because of its relatively ineffective transmission, lymphatic filarasis is seldom seen in in
casual travellers or other people with short-term exposure to the parasite. Those who
remain for longer periods in areas where transmission is intense are certainly at risk. A
large number of cases occurred among American servicemen serving in the Central
Pacific during World War 2 and other cases have occurred other military personnel,
expatriate workers, Peace Corps volunteers, missionaries, and travellers 49-52. The clinical
picture is that of acute filarial disease and microfilaraemia is extremely rare. The patient
can present with a range of signs and symptoms such as malaise, transient fevers,
lymphangitis, lymphadenopathy, skin rashes, and interestingly, episodic “black moods”
or even clinical depression. Chronic pathology does not develop unless the person
remains in the endemic area for many years.
24.3.8 Diagnosis of lymphatic filariasis
Currently, four methods for diagnosis are currently in use: detection of microfilariae,
detection of filarial antigen (only available for W. bancrofti), detection of specific
antibodies and ultrasonic detection of adult worms. For microfilariae detection, blood is
collected between 22:00 hours and midnight in areas where there is nocturnal periodicity
and between 11:00 hours and midday where there is diurnal periodicity. It must be
remembered that in lymphatic filariasis, the prepatent period - i.e. the time between
infection and the appearance of the diagnostic stages of the parasite (the microfilariae),
may be up to 12 months and is thus shorter than the incubation period (the time between
infection and the appearance of clinical symptoms). For a parasitological diagnosis of
lymphatic filariasis, the simplest method of detection is to take capillary blood from a
finger-prick and make a thick film as for malaria diagnosis. Dry the film thoroughly, stain
with Giemsa stain, and examine microscopically. A very useful variation is the “three
line method” where, instead of the blood being spread over wide area, three lines of
blood, each of 20µl are drawn on to the slide using a calibrated capillary tube. The
microfilariae per 60µl of blood are counted and the number of microfilariae per ml of
blood calculated. Thick film methods are relatively insensitive and will not detect low
numbers of microfilariae, and in situations where that is important, venous blood should
be obtained and a Knott’s concentration test done 53. This entails adding 1 ml of blood to
9 ml of 1% formaldehyde in water. The mixture is centrifuged and the deposit examined
for microfilariae.
A recent modification of the method allows for easier visualisation and counting of the
microfilariae 54. Another widely used concentration method is the membrane filter
technique whereby 1ml of blood that has been diluted in water is passed through a
cellulose filter and the microfilariae are trapped on the cellulose. The filter is then
removed from its holder, stained and examined microscopically 55. Other useful methods
for the recovery of microfilariae from the blood include the microhaematocrit
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24.10
concentration technique 56 and the use of a cytocentrifuge if one is available 57. Staining
blood films with Acridine Orange and examination under a UV microscope is another
useful survey technique58. It is also worth noting that microfilariae of W. bancrofti can
sometimes be found in the urines of patients presenting with chyluria.
There are morphological differences between microfilariae of the three species and they
can be distinguished by referring to the tables present in any book of human parasitology.
Filarial antigen tests have revolutionised the diagnosis of Bancroftian filariasis since their
introduction in the 1980’s and are now regarded as the “gold standard”. They are very
sensitive and specific, and because they are not dependent upon the presence of
microfilariae, blood can be taken at any time, and both microfilaraemic and
amicrofilaraemic cases will be detected 11,59,60. Filarial antigen tests are available in both
rapid card test and ELISA formats. The BINAX Filariasis NOW® rapid card test (also
known as the ICT test) uses capillary blood and results are available almost immediately.
This test is now the one of choice for community surveys and rapid assessment of filarial
endemicity 61,62 but there needs to be careful adherence to reading times in order to get
accurate results 63. The TropBio ELISA test (also known as the Og4C3 test) utilises
serum and is very convenient for laboratory-based studies. It is slightly more sensitive
than the rapid card test and provides a quantitative result 59,64,65. Antifilarial IgG4
antibody is produced in abundance during filarial infections and unlike broad-spectrum
IgG antibody, shows little cross reaction with non-filaroid helminths 10,11. These
antibodies are not species specific, and will not distinguish between aborted, cleared or
patent infections, but a negative antibody test strongly suggests that filarial infection is
extremely unlikely. A recently introduced antibody test called Brugia RAPID is showing
great promise as a rapid screening test for Brugian filariasis where an antigen test is not
available 66,67. PCR, and a number of other techniques are being evaluated for diagnosis
but are not yet available for routine use 10,11. The use of ultrasound to detect living adult
worms has been discussed earlier. In many patients with advanced elephantiasis all tests
for lymphatic filariasis will be negative because they no longer have any living adult
worms and reliance must be placed upon their clinical history and physical examination.
The diagnosis of expatriate cases can be particularly difficult as they very seldom become
microfilaraemic and there is little information on the value of filarial antigen tests in this
setting. Filarial antibodies should be present but they make take some time to appear. If
the patient has symptoms of acute lymphatic filariasis and tests are negative it may be
worth considering still treating the patient and observing if the symptoms disappear.
24.3.9. Control and treatment of lymphatic filariasis
In 1997, the World Assembly passed a resolution calling upon the elimination of
lymphatic filariasis as a public health problem by 2020, and in 2000, a global elimination
program was launched. The cornerstone of this program is the interruption of parasite
transmission using annual, single-dose, community-wide mass drug administration
(MDA)68. Currently, three drugs are used against lymphatic filariasis: diethylcarbamazine
(DEC), ivermectin and albendazole. All three are very effective at clearing microfilariae
and DEC and albendazole also have some effects on adult worms. Efficacy is enhanced
when a combination of drugs is used. In areas where onchocerciasis and lymphatic
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24.11
filariasis are not co-endemic, DEC at 6mg/kg plus 400mg of albendazole is the
combination of choice. In areas where lymphatic filariasis is co-endemic with
onchocerciasis or loiasis, a combination of 400mg of albendazole and 400ug/kg body
weight of ivermectin is used because DEC can cause severe reactions in patients with
Onchocerca volvulus or Loa loa. 69-76. The safety and effectiveness of MDA has been
proven to be effective in both Bancroftian and Brugian filariasis and elimination
programs are underway in a number of countries 77-82. A community compliance level of
at least 80% is required for the strategy to be effective and at least 5 annual rounds of
treatment are required. An added advantage of using albendazole and ivermectin is their
activity against soil-transmitted helminths 83. Although single-dose therapy has been
shown to be efficacious in control programs, it is not yet recommended for the treatment
of single patients who are generally given a dose of DEC at 6mg/kg every day for 12
consecutive days 84. Mild general side-reactions are common after anti-filarial treatment.
Their severity tends to be proportional to the microfilarial density and they are more
common and more severe in Brugian filariasis than in Bancroftian filariasis. Headache,
body ache, malaise, fever, nausea, urticaria are the symptoms most commonly seen, and
if they are of concern, the patient should be given analgesics. Local reactions tend to
occur over, or near to, the site of adult worms and consist of lymphadenitis, funiculitis,
epididymitis, orchitis, lymphangitis and transient lymphodema. Occasionally there may
be painful nodule formation and even abscesses. Adverse reactions seldom last for more
than three days. Severe adverse reactions that require hospitalisation are rare 81,84. The
use of DEC-medicated salt is another control strategy that has been successfully used in
several settings, most notably in China 10. Another promising chemotherapeutic strategy
is the use of antibiotics to target the endosymbiont Wolbachia bacteria that live within
some filaroids and are essential to the healthy growth and development of the parasite.
The results obtained to date are very promising. Tetracycline, doxycyline and Rifamycin
have been shown to inhibit the motility viability and release of microfilariae and impede
their development 85,86.
Control programs are very important, but those who have already developed chronic
pathology should not be over looked. As mentioned earlier a lot can be done to alleviate
the suffering caused by chronic lymphodema and elephantiasis and communities should
be encouraged to institute active home-care programs. Hydrocele can be managed by
surgery but re-occurrence can be a problem 87. The treatment for chyluria is rest and diet
rich in protein but low in fat. Surgical intervention to disconnect the route between the
leaking lymphatic vessel and the bladder has been tried in intractable cases 88. No proven
prophylactic drugs are available for lymphatic filariasis although DEC is active against
early stages of the parasite and is potentially effective. There is also a strong possibility
that doxycycline, which is used for malaria prophylaxis, may also be effective against
filarial worms by killing endosymbiont Wolbachia and research is urgently needed.
24.4
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□□□
Correspondence:
Dr Wayne Melrose, DrPH, MPH&TM, BApplSc, ThDip, FACTM, FAIMS, MNZIMLS
Acting Director, WHO Collaborating Centre for Control of Lymphatic Filariasis,
Senior Lecturer,
Anton Breinl Centre for Public Health and Tropical Medicine,
James Cook University, 4811
Townsville, Queensland, Australia
[email protected]
Professor John M. Goldsmid, BSc (Hons), MSc, PhD, FRCPath, CBiol, FIBiol, FAIBiol
FASM, Hon. FACTM, Hon. FRCPA
Emeritus Professor of Medical Microbiology
Discipline of Pathology
University of Tasmania, 7000
Hobart, Tasmania, Australia
[email protected]
***
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All rights reserved, The Australasian College of Tropical Medicine
Primer of Tropical Medicine
Enquiries to: [email protected]
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INFECTIONS OF THE LYMPHATIC SYSTEM